Sickle Cell Anemia Presence in Africa

    The inspiration of this article comes from a conversation I had today with a co-worker whose ancestry descends from Nigeria. We work in an emergency room together, our experiences today is what initiated this conversation. Sickle Cell Anemia (SCA) is a homozygous recessive trait that causes an abnormality amongst red blood cells, hemoglobin is the protein in your red blood cells that is responsible for carrying oxygen. Sickle cell anemia is common in places where malaria amongst mosquitoes is prominent, natural selection promotes family pedigree who are resistant to the malaria disease. In turn, if a person is immune malaria they unfortunately carry the sickle cell trait. This immune population can either be heterozygous or homozygous recessive. Being diagnosed with sickle cell anemia brings many potential health risks including sickle cell crisis, vaso-occlusion blood clots to digits in infants, the spleen, lungs, etc. If someone has sickle cell anemia, they are immune-compromised, if their body were to come in contact with common bacterias that cause pneumonia, or common colds, without proper medical attention these bacterias can yield fatal results. The first link of my article is a video that gives insight on the pathophysiology, potential health risks, and treatment methods of sickle cell anemia. I recommend giving it a watch, as it is quite fascinating. 

    Reflecting back on the conversation with my co-worker, she began to explain some methods countries in Africa and South-East Asia use to try to mitigate the presence of this brutal disease in their countries. In her home country, it has gotten to the point where churches will not conduct a marriage unless the genotype of the parents is confirmed. If the engaged couple runs the risk of producing offspring who can suffer from SCA, the church will not conduct the marriage. While some may regard this as unethical, the prevalence of sickle cell in their country is alarming. It is estimated about 150,000 children in Nigeria have SCA, and nearly 25% of the country are heterozygous carriers of the trait. Since there is no cure for the disease, the only way to lower these numbers is to try to prevent it from being passed on. This was a very interesting topic to me, if anyone has more insight on this please leave a comment as I would like to learn more. 

Link: https://www.youtube.com/watch?v=fIIJmg_1hv0

Link: https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-019-0376-8

Link: https://www.cdc.gov/ncbddd/sicklecell/data.html 

Methemoglobinemia causes and treatment

Methemoglobinemia is a condition that can be passed down through generations or it can be drug induced. In cases where methemoglobinemia is passed down, genes are altered which results in a deficiency of a NADH-dependent enzyme which aids in the reduction of methemoglobin. Without the presence of this enzyme, cytochromes cannot be reduced, and therefore methemoglobin cannot be reduced back to hemoglobin. In cases of methemoglobinemia, patients have too much methemoglobin in their system, decreasing the availability of oxygen throughout the body. When methemoglobinemia is drug-induced it is often reversible, but when it is passed down in families it is not. Patients will usually present with cyanosis (blue coloring of the skin) as one of the main symptoms and it can be managed.

There are a few different types of methemoglobinemia. One of which is autosomal recessive congenital methemoglobinemia (RCM) type II and new treatments are being explored since this type could result in intellectual disability, dysphagia, movement disorders, progressive decline of quality of life, and life expectancy is reduced. One treatment option that is being explored is methylene blue, which has been shown in a few studies to reduce methemoglobin with no rebound methemoglobinemia after 24 hours of dosage.

Data on methylene blue treatments is very scarce, and I think studying this treatment further would be very valuable. Since there is no current way for a full cure of methemoglobinemia that is passed down, treatments like methylene blue are the best bet for people who may be experiencing intellectual disability, dysphagia, and movement disorders. If used in babies born with the condition, I think use of methylene blue as soon as possible may help lessen the effects of having the condition. Until genes can be safely edited in humans using CRISPR-Cas9, I think methylene blue treatments will be the best and safest option for patients in the meantime.

Links:

Methemoglobinemia:
https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.2830420104

Congenital Methemoglobinemia Type II - Clinical Improvement with Short-Term Methylene Blue Treatment:
https://onlinelibrary.wiley.com/doi/epdf/10.1002/pbc.25791

How the Icefish Got Its Transparent Blood and See-Through Skull

A study from NY times have found that Antarctic blackfin icefish developed to have transparent blood to survive in the freezing water conditions. The Antarctic blackfin icefish, Chaenocephalus aceratus, lacks hemoglobin in their blood and have thin bones which makes the brain visible through its skull. Research have studied the genome of blackfin icefish to compare them to their close relatives and found that their genomic maps changed due to evolutionary time and gave the icefish to have unusual characteristics from their ancestors. The modern icefish no longer makes red blood cells and lacks hemoglobin to carry oxygen. Instead, the icefish is dedicated to make antifreeze for blood and ice-preventing proteins for survival. Since red blood cells become hard to pump and can freeze easily under freezing water, the icefish underwent a strategy for anaemia and developed supersize gills by losing it scales to absorb the abundant oxygen from the freezing water through its skin. Through evolution, the icefish also developed floppy bones that contained less minerals than their ancestors and enabled them to rise up in the water column to eat krill and other aquatic creatures that would not be found in deep sea level.

This is very amusing how the blackfin icefish lost their ancestor's features of having red blood cells and dense bones and developed different physiological features such as transparent blood and sloppy bones for adaptation. It is also very surprising to know that anaemia, a trait that is maladaptive to most vertebrates could be an advantageous trait for a different environment. 

How One Child's Sickle Cell Mutation Helped Protect the World from Malaria

Recently a study conducted by the Center of Research on Genomics and Global Health, a part of the National Institutes of Health looked into how humans obtained sickle cell anemia. This genetic mutation alters ones hemoglobin which is the molecule on the red blood cell that moves oxygen throughout the body. Roughly 7,300 years ago in Africa, scientists have found that if a person had two copies of a mutated hemoglobin gene led to the sickle cell shape attributed to the name, sickle cell anemia. However, researchers were left in a, "genetic mystery," onto why this mutation never died off. It was discovered that if a person had one mutated hemoglobin gene this allowed that individual to survive the mosquito transmitted disease, malaria, a wide spread disease in Africa at the time. Essentially, if an individual had only one copy of this allele they were safe however, if one was to have two copies of this allele, their blood cells would be defective and clog the blood vessels in the body. This discovery led researchers to believe that the development of sickle cell anemia is linked to human survival of malaria.

Article: https://www.nytimes.com/2018/03/08/health/sickle-cell-mutation.html
Original Study: http://www.cell.com/ajhg/fulltext/S0002-9297(18)30048-X

Blood Thirsty Vampire or a Blood Disorder?

According to the article on Sciencedaily,Porphyrias refers to a group of total eight known disorders. Erythropoietic protoporphyria (EPP) is also one of those known blood disorders. People who have EPP are chronically anemic, which is why they look really tired. Since they rarely come out in the sun, because of their extreme photosensitivity, they look really pale. Their skin is so sensitive that even on a cloudy day there is enough ultraviolet light to cause blistering on the exposed body parts.  Erythropoietic Protoporphyria is caused by a genetic mutation which impacts the body's ability to produce heme ( a component of the oxygen-transporting protein, hemoglobin). Protoporphyrin components start to build up in red blood cells, and plasma. Once these components are exposed to the sunlight they start creating a chemical. This chemical starts to damage the surrounding cells, which causes swelling, burning and redness in people who suffer from EPP.

According to porphyriafoundation, for the treatment of Erythropoietic Protoporphyria (EPP), a synthetic hormone called afamelanotide is used. This drug is inserted under the skin using a needle. It is released slowly over the seven days,and protects the EPP patients for about two months. The drug starts working by giving patients a tan.This tan acts like a barrier and protect them from the sun.The drug afamelanotide is allowed to use in the Europe, but is still under investigation in the united states.

This article is very interesting because it connected something fictional to something real. I love reading about new diseases, so this article caught my eye instantly. Being not able to come out in the sun and experiencing such skin conditions after being out in daylight is terrifying. However, the drug afamelanotideis helping many people and I hope it will get approved in the US too. 

Genetic Treatments for Sickle Cell

        

     Sickle cell is a condition that causes life-threatening problems in childhood. The inheritance of just one copy of the mutation somehow protected people against a different threat to survival while having two copies is lethal. It was found that sickle cell is common for people who lived in areas where malaria is present. Children born with a single mutated hemoglobin gene does not cause major problems were somehow better able than their peers to fight off malaria and would survive to deliver the gene to their future children.

A molecule of hemoglobin is made up of four subunits: most commonly two identical proteins called alpha-globins and another pair of proteins known as beta-globins. Each of these subunits contains an iron-bearing structure which can grab on to or release a molecule of oxygen. Each hemoglobin can carry up to four oxygen molecules. Individuals who inherit a single sickle-cell mutation produce one defective and one normal beta-globin; those who inherit sickle-cell genes from both parents produce only defective beta-globins.

      The only known cure for sickle-cell disease is bone marrow transplantation to provide a new circulatory system. There is another situation during development in the womb.

A fetus has a distinct kind of hemoglobin that binds very tightly to oxygen, allowing it to compete successfully with its mother's hemoglobin for oxygen in the placenta. The production of this fetal hemoglobin usually drops off, decreasing the amount of oxygen found in red blood cells. In a child who inherits the sickle-cell flaw from each parent, cells usually start to sickle several months after birth.

https://www.scientificamerican.com/article/genetic-treatments-for-sickle-cell/

https://www.nhlbi.nih.gov/health/health-topics/topics/sca

Breakthrough in Gene Therapy for Sickle Cell Disease

Breakthrough in Gene Therapy for Sickle Cell Disease

 
                                              

A team of researchers are making breakthroughs when it comes to correcting defective sickle cells with a gene-editing tool called CRISPR. This tool can fix genes that cause sickle cell, and thus can lead to promising gene therapies for this ailment.

The researchers have been able to prove that they can use such mended cells to make a “high functioning hemoglobin molecule” and have it transfer oxygen to cells. When the stem cells were placed in mice they found it successful in treating disorders such as sickle disease and thalassemia.

CRISPR is both an enzyme and “guide RNA” that can cut the part of the gene that causes mutation out and use other tools to make the correct sequence.

Sickle Cell is a disease that make normal cells turn into a sickle shape, which significantly decrease the amount the oxygen being transported around the body. This new breakthrough with CRISPR can be used to help change treatment, and detect and prevent disease in those who fall ill.

Sources:

 1       1. https://www.sciencedaily.com/releases/2016/11/161108112133.htm#